Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders.
Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders.
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DOI：
10.1007/s00213-016-4212-2
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发表时间：
2016-05
影响因子：
3.4
通讯作者：
Ferré S
中科院分区：
文献类型：
--
作者：
Ferré S
咖啡因的精神兴奋剂特性进行审查，并与原型精神兴奋剂，能够导致物质使用障碍（SUD）。咖啡因能产生精神上的激活、强化和唤醒作用，这取决于它能解除内源性腺苷对多巴胺和唤醒系统的抑制。一个模型，认为纹状体腺苷A2 A-多巴胺D2受体异聚体作为多巴胺依赖性纹状体功能的关键调制器（奖励导向的行为和学习的刺激奖励和奖励反应协会）的介绍，这应该解释大多数的精神和咖啡因的强化作用。该模型可以解释咖啡因诱导的旋转行为在大鼠单侧纹状体多巴胺去神经和咖啡因的能力，以扭转在多巴胺缺乏的啮齿类动物的adipsic-aphagic综合征。该模型还可以解释较弱的强化效果和低滥用倾向的咖啡因，与原型精神兴奋剂。最后，该模型可以解释咖啡因的实际主要社会危害：咖啡因能够增强滥用药物的成瘾性和毒性作用，尤其是咖啡因的惊人关联（作为掺假物）与可卡因、安非他明衍生物和合成卡西酮以及与酒精混合的能量饮料;儿童和青少年对咖啡因的精神刺激作用的敏感性更高，并可能增加发展SUD的脆弱性。纹状体A2 A-D2受体异聚体构成了咖啡因明确的主要药理学靶点，并提供了咖啡因增强原型精神兴奋剂的急性和长期作用的主要机制。
The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants, able to cause substance use disorders (SUD). Caffeine produces psychomotor activating, reinforcing and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. A model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives and synthetic cathinones and energy drinks with alcohol; and the higher sensitivity of children and adolescents to the psychostimulants effects of caffeine and its possible increase in the vulnerability to develop SUD. The striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.